Multiple sclerosis (MS) is often referred to as an autoimmune disease. Although the body’s immune system is involved in the development of MS and most scientists consider it to be an autoimmune disease, some people question the autoimmune component of MS. This article discusses why some researchers claim MS is not an autoimmune disease and explores the aspects of the disease that are autoimmune.

What Is the Argument Against MS as an Autoimmune Disease?

A condition must meet many criteria to be classified as an autoimmune disease. One of the criteria that a disease must fulfill is the presence of an immune response against one or more autoantigens common among all the people living with the condition (a ubiquitous autoantigen).

Much of the argument against MS as an autoimmune disease relates to the autoantigens associated with the disease. Antigens are substances that are recognized by the immune system as an invader or foreign. The term autoantigen (or self-antigen) is used when the substance recognized by the immune system as an invader originates from the body’s cells and tissues.

Scientists can measure the immune response against an autoantigen by looking for cells that specifically recognize the autoantigen. The immune cells that are normally analyzed for this include B cells and T cells. Scientists will perform an analysis to see if a T cell reacts to an autoantigen by analyzing its T-cell receptor (TCR). The TCR is the receptor that binds antigens and autoantigens. The TCR also contributes to the activation of the T cell.

For B cells, scientists will look for something called an autoantibody in the blood and cerebrospinal fluid in the spinal canal. These autoantibodies are made and secreted by B cells and will bind to autoantigens.

When it comes to the autoantigens associated with MS, many have been identified for T cells and B cells. These include molecules called myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein. These autoantigens are derived from the protective myelin sheath that covers nerve fibers in the central nervous system (CNS). It can also be present in other cell types in the CNS, including neurons, astrocytes, and oligodendrocytes.

Scientists and neurologists do not always find the same pattern of immune response among people living with MS. This information creates the argument against MS being classified as an autoimmune disease. It also influences some people to refer to it as an immune-mediated disease instead.

Is There Evidence That MS Is Autoimmune?

Although the ubiquitous — or universal — antigen has not been identified for MS, there are still many components of the disease that suggest it is autoimmune. Evidence for the autoimmune activity in MS also implies it is an immune-mediated disease. Here is some evidence that supports these statements:

• Genetic and environmental risk factors
• Immune system activity in MS
• Immune-modulating therapies for MS

Genetic and Environmental Risk Factors

The exact cause of MS is unknown. However, scientists believe there are some environmental and genetic risk factors associated with developing the disease. Many of these factors are associated with the immune system. For example, a person who expresses a particular version of a gene called HLA-DRB1*15:01 is three times more likely to develop the disease. This gene is important for activating T cells in the immune system.

Environmental factors, such as infection with certain viruses, also put a person at a higher risk of developing MS. It is thought that these infections might activate the immune system to begin attacking the body’s tissues. Although it is not known how these infections activate the immune system to attack the body, scientists believe this may play a role in the development of MS.

Immune System Activity in MS

Scientists have isolated B cells and T cells from people living with MS that are specific and reactive against autoantigens. They have also identified autoantibodies in the blood of individuals living with MS. Additionally, when they analyze the function of the immune cells of people living with MS, the cells are often dysfunctional. For example, a subset of T cells known as regulatory T cells are supposed to suppress the immune system and prevent autoimmune activity. Studies have shown that these regulatory T cells are dysfunctional and do not properly suppress the immune system in people with MS.

Scientists have also found T cells, B cells, and another immune cell type called a macrophage in active lesions in the brain and spinal cord. This finding suggests that these immune cells may be participating in the destruction that occurs to the CNS during an MS attack.

Immune-Modulating Therapies for MS

Many of the treatments for MS work by suppressing the immune system or by preventing it from attacking the CNS. This includes the use of corticosteroids, which can suppress inflammation and immune cell activity. Corticosteroids are typically given quickly at the onset of a symptom-worsening flare or a true relapse.

Therapies that deplete immune cells, such as B cells, with Ocrevus (ocrelizumab) have also been effective. Rituxan (rituximab) is another example of a medication for MS that specifically targets the immune system. Suppressing the immune system during an MS flare helps improve disease outcomes, which provides additional evidence that the immune system is involved in the development of MS.

Understanding the Immune System and MS

MS is a disease in which the immune system attacks the CNS. This leads to the demyelination of nerve cells and the development of symptoms associated with the disease. Some people debate whether the diagnosis of multiple sclerosis is a true autoimmune disease. However, the dysfunction of the immune system during this condition is clear, and the immune system certainly plays a role. As technology advances for screening and identifying B cells and T cells reactive against autoantigens, scientists may identify the universal autoantigen associated with MS. Nonetheless, features of MS suggest this condition is an autoimmune disease.

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